Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Effects of exercise modalities on central hemodynamics, arterial stiffness and cardiac function in cardiovascular disease: Systematic review and meta-analysis of randomized controlled trials

  • Yahui Zhang ,

    Contributed equally to this work with: Yahui Zhang, Lin Qi

    Roles Investigation, Methodology, Resources, Software, Validation, Writing – original draft

    Affiliation Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, China

  • Lin Qi ,

    Contributed equally to this work with: Yahui Zhang, Lin Qi

    Roles Methodology, Resources, Validation, Writing – review & editing

    Affiliation Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, China

  • Lisheng Xu ,

    Roles Methodology, Resources, Supervision, Validation, Writing – review & editing

    xuls@bmie.neu.edu.cn

    Affiliations Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, China, Key Laboratory of Medical Image Computing, Ministry of Education, Northeastern University, Shenyang, Liaoning, China

  • Xingguo Sun,

    Roles Resources, Supervision, Validation, Writing – review & editing

    Affiliation Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Beijing, China

  • Wenyan Liu,

    Roles Methodology, Resources, Validation

    Affiliation Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, China

  • Shuran Zhou,

    Roles Methodology, Resources

    Affiliation Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, China

  • Frans van de Vosse,

    Roles Methodology, Supervision, Writing – review & editing

    Affiliations Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, China, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands

  • Stephen E. Greenwald

    Roles Resources, Visualization, Writing – review & editing

    Affiliation Blizard Institute, Barts & The London School of Medicine &Dentistry, Queen Mary University of London, London, United Kingdom

Effects of exercise modalities on central hemodynamics, arterial stiffness and cardiac function in cardiovascular disease: Systematic review and meta-analysis of randomized controlled trials

  • Yahui Zhang, 
  • Lin Qi, 
  • Lisheng Xu, 
  • Xingguo Sun, 
  • Wenyan Liu, 
  • Shuran Zhou, 
  • Frans van de Vosse, 
  • Stephen E. Greenwald
PLOS
x

Abstract

Background

Exercise is accepted as an important contribution to the rehabilitation of patients with cardiovascular disease (CVD). This study aims to better understand the possible causes for lack of consensus and reviews the effects of three exercise modalities (aerobic, resistance and combined exercise) on central hemodynamics, arterial stiffness and cardiac function for better rehabilitation strategies in CVD.

Methods

The electronic data sources, Cochrane Library, MEDLINE, Web of Science, EBSCO (CINAHL), and ScienceDirect from inception to July 2017 were searched for randomized controlled trials (RCTs) investigating the effect of exercise modalities in adult patients with CVD. The effect size was estimated as mean differences (MD) with 95% confidence intervals (CI). Subgroup analysis and meta-regression were used to study potential moderating factors.

Results

Thirty-eight articles describing RCTs with a total of 2089 patients with CVD were included. The pooling revealed that aerobic exercise [MD(95%CI) = -5.87 (-8.85, -2.88), P = 0.0001] and resistance exercise [MD(95%CI) = -7.62 (-10.69, -4.54), P<0.00001] significantly decreased aortic systolic pressure (ASP). Resistance exercise significantly decreased aortic diastolic pressure [MD(95%CI) = -4(-5.63, -2.37), P<0.00001]. Aerobic exercise significantly decreased augmentation index (AIx) based on 24-week exercise duration and patients aged 50–60 years. Meanwhile, aerobic exercise significantly improved carotid-femoral pulse wave velocity (cf-PWV) [MD(95%CI) = -0.42 (-0.83, -0.01), P = 0.04], cardiac output (CO) [MD(95% CI) = 0.36(0.08, 0.64), P = 0.01] and left ventricular ejection fraction (LVEF) [MD(95%CI) = 3.02 (2.11, 3.93), P<0.00001]. Combined exercise significantly improved cf-PWV [MD(95%CI) = -1.15 (-1.95, -0.36), P = 0.004] and CO [MD(95% CI) = 0.9 (0.39, 1.41), P = 0.0006].

Conclusions

Aerobic and resistance exercise significantly decreased ASP, and long-term aerobic exercise reduced AIx. Meanwhile, aerobic and combined exercise significantly improved central arterial stiffness and cardiac function in patients with CVD. These findings suggest that a well-planned regime could optimize the beneficial effects of exercise and can provide some evidence-based guidance for those involved in cardiovascular rehabilitation of patients with CVD.

Introduction

Cardiovascular disease (CVD) is the leading cause of death and the main risk factor for world-wide morbidity [1, 2]. According to the World Health Organization global status report on Non-communicable Diseases (NCD) in 2014, 38 million of the world’s 56 million deaths are from NCDs. Figures from the same report suggest that in 2012 an estimated 17.5 million (46%) of these deaths are due to CVD. Of these deaths from CVD, heart attacks are responsible for 7.4 million, and stroke, for 6.7 million [3]. Therefore, low-cost and effective prevention and treatment are urgently needed.

Insufficient physical activity is considered the fourth leading risk factor for global deaths, and in 2010, was responsible for 69.3 million Disability Adjusted Life Years (DALYs) [3, 4]. Regular physical activity is accepted as an important contribution to the prevention and rehabilitation of CVD [5, 6]. Exercise-based cardiac rehabilitation (aerobic endurance training, dynamic resistance training and both in combination) have been used to manage cardiovascular health in individuals with CVD [6].

Central hemodynamics and arterial stiffness have been recognized as strong independent predictors of all-cause mortality of cardiovascular (CV) events [79]. These parameters, such as central blood pressure, augmentation index (AIx) and carotid-femoral pulse wave velocity (cf-PWV)) were used to evaluate the exercise-based rehabilitation of patients with CVD [1012]. Previous meta-analyses have reported the effects of exercise training on arterial stiffness. However, these analyses mainly focused on a range of adult subjects, including patients with CVD, diabetes, obesity and healthy people [13, 14]; or the effect of one type of exercise training (such as aerobic or resistance exercise) on arterial stiffness [10, 15, 16].

In addition, some studies have investigated the effect of two or three types of exercise training on central hemodynamics and arterial stiffness. Croymans et al. found that aortic systolic blood pressure was decreased, while AIx and cf-PWV were not altered in response to high-intensity resistance exercise [17]. Ashor et al. concluded that AIx and PWV were significantly reduced with aerobic exercise, while resistance or combined exercise had no significant effect on these variables [13]. Figueroa found that resistance exercise had no clear cut effects on central blood pressure and wave reflection in obese adults with prehypertension [18]. There was no consensus about the effects of different exercise modalities on the central hemodynamic and central arterial stiffness variables.

Moreover, central hemodynamics and central arterial stiffness are closely related to cardiac function [19, 20]. Arterial stiffness, central hemodynamics and cardiac function contribute to the complex pathophysiological mechanism of CVD. Increased arterial stiffness (as expressed by PWV) leads to early arrival at the heart of reflected waves from peripheral sites, resulting in augmentation of central systolic pressure. This augmentation of central systolic pressure can lead to adverse changes in cardiac function such as elevation of left ventricular afterload and decreased coronary perfusion [2123], which may in turn, lead to left ventricular hypertrophy and myocardial ischemia [23, 24]. Previous studies have investigated these changes and reported the effects of exercise training on arterial stiffness/central hemodynamics, cardiac output (CO) and left ventricular ejection fraction (LVEF) in patients with CVD. However, it was controversial for the effects of exercise training on these parameters in CVD. Kitzman et al. found that exercise training did not increase the ejection duration (EF) or improve arterial stiffness [25], and Chrysohoou et al. showed that PWV and LVEF was not improved in response to combined exercise [26]. On the other hand, Molmen-Hansen et al. found that aerobic exercise increased CO, LVEF, and decreased blood pressure and total peripheral resistance (TPR) in patients with hypertension [27]. Understanding of the effects of different exercise training on the central hemodynamics, central arterial stiffness and cardiac function merits comprehensive analysis and evaluation.

Therefore, this systematic review and meta-analysis aimed to investigate the effect of different exercise modalities on central hemodynamics, central arterial stiffness and cardiac function in patients with CVD. Additionally, this meta-analysis provided an overall assessment of effect of different exercise modalities on cardiovascular system to evaluate the possible causes for aforementioned lack of consensus.

Methods

Protocol and registration

This meta-analysis was performed according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A completed PRISMA checklist was shown in S1 Text. The protocol of this study has been recorded in http://www.crd.york.ac.uk/PROSPERO. PROSPERO registration number: CRD42016052379.

Search strategy.

The search for relevant studies was performed via electronic searches of five databases (Cochrane Library, MEDLINE, Web of Science, EBSCO (CINAHL), and ScienceDirect from their inception to July 2017). This meta-analysis was only limited to RCTs. The electronic search strategies for all databases are provided in S2 Text. We also searched for eligible articles in reference citation of reviews and research articles.

Inclusion criteria.

  1. Types of studies: Only published RCTs were covered in this meta-analysis.
  2. Types of participants: Patients (aged> = 18 years) with CVD were considered, including those with heart pathology (such as coronary artery disease, heart failure, acute myocardial infarction, etc.), hypertension and cerebrovascular disease (stroke).
  3. Types of interventions: Patients (exercise-rehabilitation group) undergoing aerobic exercise, resistance exercise, and combined exercise were considered. Control groups (non-exercise group) included those with a sedentary life style and those having some life-style education. In addition, subjects who had had exercise intervention were included if they had been assigned to a control group and compared to others who had undertaken more strenuous exercise.
  4. Types of outcome measures: These included central hemodynamic variables (e.g., aortic systolic pressure (ASP), aortic diastolic pressure (ADP), AIx), central arterial stiffness, as expressed by cf-PWV and cardiac function (CO and LVEF).

Selection of studies.

The same selection criteria were independently used by two authors to screen the titles, abstracts and full texts of relevant studies. Articles that did not meet the inclusion criteria were removed including reviews, non-RCTs, those investigations with only healthy participants, and patients without CVD, CVD with serious arrhythmia or unstable angina, serious aortic stenosis, serious congestive heart failure or pulmonary hypertension with exercise contraindication, less than aerobic exercise intensity, exercise durations with less than 4 weeks, non-exercise intervention, no control groups and non-central hemodynamic or arterial stiffness or cardiac function variables. Any disagreement was discussed or arbitrated by a third author.

Data extraction and management.

The following information was extracted: study characteristics (e.g., article, year and country), participant characteristics (e.g., age and sample size of different groups), disease type, intervention description, trial period, outcome measures and exercise duration (period of exercise intervention). The two authors who selected the articles also extracted and managed the information therein. Any disagreement was discussed or arbitrated by a third author.

Quality assessment.

The PEDro scale [28] was used to assess the risk of bias for inclusion in this meta-analysis. This is a free database of randomized trials, systematic reviews and clinical practice guidelines in physiotherapy. The methodological quality of each article was independently evaluated by the two reviewing authors using a total scale (11-item). The following information was assessed: eligibility criteria, point estimates and variability, between-group comparisons, intention-to-treat analysis, adequate follow-up, blinded assessors, blinded subjects, blinded therapists, baseline comparability, concealed allocation and random allocation. When a disagreement occurred, a third author was consulted.

Statistical analysis.

This meta-analysis used the Review Manager Software (RevMan 5.3) and stata12.0 to analyze data. The I2 statistic and the chi-square test were used to assess the heterogeneity of the included articles. There was significant heterogeneity when p>0.1 when using the Cochrane Q statistic in the forest plot. The consistency between studies was evaluated by I2, and risk (low, moderate and high) of heterogeneity was categorized by I2<25%, I2 = 25%-75% and I2>75%, respectively [29]. The outcome measures of each study were combined by meta-analysis using a fixed effects model or random effects model. Given that all the variables from the included articles were continuous, the standardized mean difference (SMD) or the mean difference (MD) and the 95% confidence interval (CI) were used to analyze the studies. Mean and standard deviation (SD) of the variables measured in the RCTs from before and after exercise were included in the forest plots. If the continuous data were summarized by median and interquartile range (IQR), SD was computed as SD = IQR/1.35 [30]. The SD also could be obtained from the equation: , where SE is the standard error, and N is the number of participants. P<0.05 was considered as statistically significant [30]. Sensitivity analysis was performed by removing each inclusion article to assess the quality and consistency of results. Subgroup analyses were conducted to investigate the effect of different exercise modalities (aerobic, resistance and combined exercise) on central hemodynamics, arterial stiffness and cardiac function, respectively. Subgroup analyses were also performed to explore the source of heterogeneity according to age, disease, exercise duration and gender. Meta-regression was used to explore the relationships between study characteristics (such as age, disease, exercise duration and gender) and cardiovascular variables by using Stata software (version 12.0). In addition, funnel plot asymmetry estimation was conducted to evaluate possible publication bias using Egger’s regression test [31].

Results

Search results

A flow chart describing the selection process is shown in Fig 1. One hundred and fifteen potentially eligible articles were identified from MEDLINE, Web of Science, the Cochrane library, EBSCO and ScienceDirect. After reviewing the full content of these articles, thirty-eight articles satisfied the inclusion criteria. Seventy-seven were excluded for the following reasons: patients free of CVD, non-randomized controlled trials, review articles, other chronic disease (such as chronic kidney disease, type 2 diabetes or rheumatoid arthritis), articles having irrelevant outcomes (such as peripheral circulatory variables), or interventions affecting the control group (such as diet or drug) which made them unsuitable. The basic characteristics of each study are summarized in Table 1. The thirty-eight included articles [11, 2527, 3265] covered 2089 patients with CVD (22 articles with heart disease, 13 with hypertension, and 3 with cerebrovascular disease). The distribution of articles by country of publication was: United States (n = 11, 28.95%), the United Kingdom (n = 3, 7.9%), Canada (n = 3, 7.9%), Italy (n = 4, 10.53%), China (n = 3, 7.9%), Brazil (n = 1, 2.63%), Germany (n = 2, 5.26%), South Korea (n = 1, 2.63%), Denmark (n = 1, 2.63%), Turkey (n = 2, 5.26%), Australia (n = 1, 2.63%), Portugal (n = 1, 2.63%), Greece (n = 1, 2.63%), Norway (n = 1, 2.63%), Belgium (n = 1, 2.63%), Poland (n = 1, 1. 2.63%), and Switzerland (n = 1, 2.63%).

Risk of bias of the selected studies.

The risk of bias of the selected studies was evaluated by the PEDro scale (Table 2). The eligibility criteria, blind assessors and adequate follow-up were reported in 27 articles (71.05%), 17 articles (44.74%) and 28 articles (73.68%), respectively. Random allocation, baseline comparability, between-group comparison and point estimates and variability were reported in 38 articles (100%), 37 articles (97.37%), 36 articles (94.74%) and 36 articles (94.74%), respectively. Concealed allocation and intention to treat analysis were carried out in 4 (10.53%) and 9 articles (23.68%), respectively. In addition, there were no articles involving blinded subjects and blinded therapists.

Effect of different exercise modalities on the central hemodynamics—Aortic systolic pressure (ASP).

Based on a fixed effects model, ASP was significantly improved by aerobic exercise [MD (95% CI) = -5.87 (-8.85, -2.88), P = 0.0001] and resistance exercise [MD (95% CI) = -7.62 (-10.69, -4.54), P<0.00001] for the exercise group when compared to the control group (Table 3 and Fig 2). There was no reduction in ASP in subjects undertaking combined exercise in patients with CVD [MD (95% CI) = -3.82 (-13.07, 5.43), P = 0.42] in this subgroup analysis due to one included study. Subgroup analyses of aerobic exercise according to age, disease, exercise duration and gender were listed in Table 4.

thumbnail
Table 4. Subgroup analyses and meta-regression of effect of aerobic exercise on the central hemodynamics, arterial stiffness and cardiac function according to age, disease, exercise duration and gender.

https://doi.org/10.1371/journal.pone.0200829.t004

thumbnail
Fig 2. Forest plot of the change in aortic systolic pressure (ASP) in the exercise and control groups.

Subgroups correspond to the exercise modalities. Squares represent the MD for each trial, and diamonds represent the pooled MD in ASP across trials. SD = standard deviation; IV = inverse variance; 95% CI = 95% confidence intervals.

https://doi.org/10.1371/journal.pone.0200829.g002

Aortic diastolic pressure (ADP).

Using a fixed effects model, ADP was not significantly improved by aerobic exercise [MD (95% CI) = 0.06 (-2.19, 2.31), P = 0.96] or combined exercise [MD (95% CI) = -4.2 (-11.49, 3.09), P = 0.26] (Table 3 and Fig 3). However, Resistance exercise was found to reduce ADP by 4 mmHg [MD (95% CI) = -4 (-5.63, -2.37), P<0.001] for the exercise group when compared to the control group (Table 3 and Fig 3). Subgroup analyses of aerobic exercise according to age, disease, exercise duration and gender were reported in Table 4.

thumbnail
Fig 3. Forest plot of the change in aortic diastolic pressure (ADP) in the exercise and control groups.

Subgroups correspond to the exercise modalities. Squares represent the MD for each trial, and diamonds represent the pooled MD in ADP across trials. SD = standard deviation; IV = inverse variance; 95% CI = 95% confidence intervals.

https://doi.org/10.1371/journal.pone.0200829.g003

Augmentation index (AIx).

A random effects model was selected as there were larger fluctuation of the variance between each included study in AIx. There was no significant difference in AIx after aerobic and resistance exercise in CVD, while there was a significant difference in AIx after combined exercise in this subgroup analysis due to one included study (Fig 4 and Table 3). Subgroup and regression analyses of effect of aerobic exercise on AIx were conducted according to age, disease, exercise duration and gender (Table 4). AIx was significantly decreased by 24-week aerobic exercise [MD (95% CI) = -12.00 (-19.92, -4.08), P = 0.003] or in patients aged 50–60 years [MD (95% CI) = -8.13 (-14.31, -1.95), P = 0.01]. AIx was significantly increased with combined exercise in patients with chronic heart failure (CHF) when compared to a control group with one included study. According to the meta-regression analysis, AIx was not affected by age (P = 0.981), gender (P = 0.703), disease (P = 0.206) and exercise duration (P = 0.133). In this meta-analysis, of 10 trials (aerobic exercise) that measured AIx, only 4 studies (152) reported heart rate-adjusted AIx. This result found that there was no significant difference [MD (95% CI) = 2.95 (-0.77, 6.67), P = 0.12] in heart rate-adjusted AIx after aerobic exercise (S1 Fig).

thumbnail
Fig 4. Forest plot of the change in central augmentation index (AIx) in the exercise and control groups.

Subgroups correspond to the exercise modalities. Squares represent the MD for each trial, and diamonds represent the pooled MD in AIx across trials. SD = standard deviation; IV = inverse variance; 95% CI = 95% confidence intervals.

https://doi.org/10.1371/journal.pone.0200829.g004

Effect of different exercise modalities on central arterial stiffness—Carotid-femoral pulse wave velocity (cf-PWV).

There was a significant change in cf-PWV in response to aerobic exercise [MD (95% CI) = -0.42 (-0.83, -0.01), P = 0.04] and combined exercise [MD (95% CI) = -1.15 (-1.95, -0.36), P = 0.004] in patients with CVD, using a fixed effects model. However, no significant difference was found after resistance exercise [(MD (95% CI) = -0.26 (-0.72, 0.20), P = 0.27] for the exercise group compared with the control group (Table 3 and Fig 5). The result (mean difference or 95%CI or test for overall effect) was affected by one study [26] for cf-PWV after combined exercise in this sensitivity analysis. Therefore, this meta-analysis may provide weak evidence of the effect of combined exercise on cf-PWV. Subgroup analyses of aerobic exercise according to age, disease, exercise duration and gender were listed in Table 4.

thumbnail
Fig 5. Forest plot of the change in carotid-femoral pulse wave velocity (cf-PWV) in the exercise and control groups.

Subgroups correspond to the exercise modalities. Squares represent the MD for each trial, and diamonds represent the pooled MD in cf-PWV across trials. SD = standard deviation; IV = inverse variance; 95% CI = 95% confidence intervals.

https://doi.org/10.1371/journal.pone.0200829.g005

Effect of different exercise modalities on cardiac function—Cardiac output (CO).

Using a fixed effects model, seven studies with 372 patients were included to evaluate the effect of exercise on CO. Aerobic exercise and combined exercise were found to increase CO by 0.36 L/min [MD (95% CI) = 0.36 (0.08, 0.64), P = 0.01] and 0.9 L/min [MD (95% CI) = 0.9 (0.39, 1.41), P = 0.0006] in the exercise group when compared to the control group (Table 3 and Fig 6), respectively. However, CO was not significantly improved by resistance exercise in patients with CVD [MD (95% CI) = -0.02 (-0.6, 0.56), P = 0.95]. Subgroup analyses of aerobic exercise according to age, disease, exercise duration and gender were reported in Table 4. Age and disease affected the change of CO after aerobic exercise.

thumbnail
Fig 6. Forest plot of the change in cardiac output (CO) in the exercise and control groups.

Subgroups correspond to the exercise modalities. Squares represent the MD for each trial, and diamonds represent the pooled MD in CO across trials. SD = standard deviation; IV = inverse variance; 95% CI = 95% confidence intervals.

https://doi.org/10.1371/journal.pone.0200829.g006

Left ventricular ejection fraction (LVEF).

This meta-analysis of nineteen studies with 843 patients, using a fixed effects model, showed that aerobic exercise increased LVEF [MD (95% CI) = 3.02 [2.11, 3.93], P<0.00001], when compared to non-exercising controls (Table 3 and Fig 7). No significant difference was found after resistance exercise [MD (95% CI) = 2 (-3.26, 7.26), P = 0.46] or combined exercise [MD (95% CI) = 0.79 (-1.18, 2.77), P = 0.43] (Table 3 and Fig 7). A sensitivity analysis was conducted for LVEF after aerobic exercise, and the significance of the difference between the exercise and control groups was not changed when studies were removed 1 by 1. Meta-regression was used to explore the higher heterogeneity (I2 = 48%) and showed evidence of a relationship between mean difference of LVEF and age, for patients with CVD (Beta = -3.47, P = 0.000, Fig 8A and Table 4), while mean difference of LVEF was not related to changes of exercise duration (Beta = 0.59, P = 0.389, Fig 8B and Table 4), disease (Beta = -0.55, P = 0.954, Table 4) and gender (Beta = 1.96, P = 0.276, Table 4).

thumbnail
Fig 7. Forest plot of the change in left ventricular ejection fraction (LVEF) in the exercise and control groups.

Subgroups correspond to the exercise modalities. Squares represent the MD for each trial, and diamonds represent the pooled MD in LVEF across trials. SD = standard deviation; IV = inverse variance; 95% CI = 95% confidence intervals.

https://doi.org/10.1371/journal.pone.0200829.g007

thumbnail
Fig 8. Meta-regression for exploring heterogeneity in LVEF.

(A) The association between mean difference of left ventricular ejection fraction (LVEF) and different age groups with CVD. (B) The association between mean difference of left ventricular ejection fraction (LVEF) and aerobic exercise intervention of different exercise durations. (The shaded areas represent the range of confidence interval; size of the circles indicates sample size).

https://doi.org/10.1371/journal.pone.0200829.g008

Publication bias

There was no publication bias for ASP (asymmetry test P = 0.068), ADP (asymmetry test P = 0.352), CO (asymmetry test P = 0.189), AIx (asymmetry test P = 0.561) LVEF (asymmetry test P = 0.102) and cf-PWV (asymmetry test P = 0.07) according to the results of Egger’s regression test.

Discussion

This meta-analysis, which gathered 2089 patients with CVD from 38 articles, provides evidence of the effects of exercise and differences between three types of exercise on central hemodynamics, central arterial stiffness and cardiac function. The results suggest that in patients with CVD, aerobic exercise significantly improved ASP, cf-PWV, CO and LVEF. Resistance exercise significantly reduced ASP and ADP. Combined exercise significantly improved cf-PWV and CO in patients with CVD.

We have not found any meta-analysis or systematic review that had evaluated the effects of different exercise modalities on central hemodynamics, arterial stiffness and cardiac function of patients with CVD, and therefore there was no systematic description of evidence for these differences. Previous studies have focused primarily on either aerobic or resistance exercise rather than combined, or have considered only a few measures of arterial stiffness but not those associated with central blood pressure, AIx and cardiac function. In this study, only RCTs of patients with CVD were included, and the impact of these two types of exercise, both singly and combined, on a wider range of cardiovascular variables were investigated. Therefore, this study provides a broader evaluation of the effects of different exercise modalities on central hemodynamics, central arterial stiffness and cardiac function in patients with CVD as well as their application for the rehabilitation of CVD.

In this meta-analysis, we observed significant changes, in response to aerobic and resistance exercise, in central BP, (this being more predictive for target organ damage), cardiovascular morbidity and mortality in comparison with brachial BP [66, 67] in patients with CVD. However, there was no significant difference in ASP or ADP after combined exercise in this subgroup analysis due to one included study [56]. Previous studies have supported the notion that aerobic or resistance exercise reduces ASP due to improvements in vasoactive substances and endothelial function [17, 18, 37, 68], and agreed that there was no significant difference in ADP with aerobic exercise [59]. However, a study showed unfavorable effect of resistance exercise on central blood pressure and arterial compliance [69]. The high blood pressure in response to resistance exercise may be mainly related to arterial stiffness [70]. At the same time, increased arterial stiffness was associated with the promotion of vascular smooth muscle cell growth and inflammatory cytokines, increasing the central blood pressure [71]. However, several other mechanisms for the favorable effect of resistance exercise on central blood pressure have been proposed. Croymans et al. suggested that the beneficial effect of resistance exercise on central blood pressure is due to improved endothelial function and microvascular perfusion [17]. Whereas, Heffernan et al. found that resistance exercise significantly improved central blood pressure because of its impact on the reservoir pressure, which is proportional to the volume of blood stored in the aorta, and which in turn depends on the interactions of systemic arterial compliance and impedance to outflow [11, 72]. However, Figueroa and Taaffe reported that it may be attributed to improved peripheral muscular artery dilation and peripheral vascular resistance (PVR) [18, 68]. The reductions of PVR and arteriolar tone with resistance exercise may change terminal impedance enabling greater runoff into peripheral microvascular beds during diastole (inflow< outflow) resulting in sustained reductions in reservoir pressure [72]. In the subgroup analysis of different exercise modalities, only one included study investigated effect of combined exercise on central blood pressure, with a weak evidence for this effect. Additionally, although there was no significant difference in effect of combined exercise on ASP due to one limited study (P = 0.42), different exercise modalities significantly decreased ASP according to the overall effect of total subgroup (P<0.00001).

In this study, subgroup analysis and meta-regression analysis of studies (effect of aerobic exercise on AIx) were conducted according to age, disease, exercise duration and gender. AIx was significantly decreased in response to 24-weeks aerobic exercise or in patients aged 50–60 years. However, the change of AIx was not affected by gender, disease and HR after aerobic exercise intervention. The previous work found that different durations and different age were associated with the effect of exercise training on the cardiovascular health [73]. In addition, some studies also reported that AIx may be influenced by age or disease, as arterial reservoir pressure increases rapidly with age and disease [74, 75]. Furthermore, AIx may be affected by other factors including LV afterload, exercise intensity, frequency and duration, central wave reflection, forward wave genesis and impedance [11, 13, 75, 76]. AIx was not only affected by wave reflection from pulse wave, but also affected by compliant properties of elastic arteries [77]. Combined exercise significantly increased AIx in patients with CHF in only one included study [26]. We found that aerobic exercise with resistance exercise just improved the aerobic capacity of patients with CHF [78], while a study found that increased AIx was related to improved ventricular-aortic coupling in response to combined exercise, and increased AIx and PWV can reveal the improved arterial function [26]. In this report, the result may be influenced by the fact that only one study [26] was included. Therefore, future experimental studies should investigate the AIx of patients with CHF in response to combined exercise.

This meta-analysis also reveals that aerobic and combined exercise significantly improved cf-PWV in patients with CVD. Our findings agree with those of some studies that aerobic exercise decreased cf-PWV in CVD patients or in all adults [1315], and found that improved cf-PWV with aerobic exercise may be related to increased nitric oxide (NO) availability, higher conduit artery elastin content, decreased concentration of vasoconstrictor agents, increased oxygen uptake (VO2) peak and reduction in ASP [13, 43]. However, our findings did not agree with those of previous studies which reported no significant effect of aerobic training on PWV in patients with acute myocardial infarction (MI) due to the limited exercise duration [10, 59]. In addition, some studies have reported that cf-PWV was not improved in hypertensive subjects or in patients with chronic kidney disease in response to aerobic exercise because of the high level of blood pressure regulated by sympathetic nervous system [10, 79]. Combined exercise also significantly improved cf-PWV in patients with CVD in this study. Our findings support those of Li et al. [80] that combined exercise may have favorable effect on arterial stiffness when aerobic and resistance exercise take place in the same exercise session. However, this contrasts with previous meta-analyses which found no significant difference in PWV with combined exercise [13, 14]. These meta-analyses pooled the results from subjects with disparate conditions (some were healthy, others were obese and others were CVD patients). Furthermore, peripheral and central arterial stiffness data were pooled. Montero et al. [10, 14] included non-randomized controlled trials in their analysis. We emphasize that, in this study the response of central hemodynamic variables to different exercise modalities were comprehensively evaluated, and we restricted our analysis to RCTs of patients with CVD. The different results from these meta-analyses may be related to small number of studies in subgroup analysis. In addition, Montero et al. found that cf-PWV did not decrease with combined exercise due to the limitation of resistance exercise component [14]. It was controversial and complex for effects of resistance exercise on cf-PWV [16, 17], and the effects of resistance were not only associated with exercise intensity and healthy status, but also with the changes of arterial compliance and central blood pressure regulated by sympathetic nervous system activity, and protein synthesis regulating muscle mass [14, 16, 80, 81].

Aerobic exercise also significantly improved LVEF, and both aerobic exercise and combined exercise significantly improved CO in patients with CVD. However, there was no significant difference in LVEF in response to resistance exercise. A previous meta-analysis has shown that aerobic exercise improved EF, and reversed LV remodeling in patients with HF, while the benefit was not evident with combined exercise and resistance exercise [82]. In this study, meta-regression showed that the effects of aerobic exercise on LVEF were associated with age. LVEF is significantly increased with aerobic exercise due to its impact on the release of vasoconstrictive neurohormones, hemodynamic loading, peak exercise stroke volume (SV), myocardial contractility and diastolic filling [12, 8284]. The increased SV with exercise was associated with a reduction in TPR driven by sympathetic activity and vagal tone [85]. At the same time, myocardial contractility contributed to the increased SV in response to exercise training [84]. It was controversial whether resistance training had any beneficial effect on LVEF. Some studies found that it may be associated with increased systolic and diastolic pressure loading, while others found that it may increase LV wall stress with resistance exercise leading to decreased LV wall stress and contractile and preload reserve [12]. This study supported the findings of the previous ones that CO was significantly increased with aerobic exercise because of improved VO2 peak related to oxygen delivery and decreased TPR, HR and SV contributing to cardiac performance, and ventricular filling [48, 79, 86].

Although this meta-analysis has reported some novel findings concerning the disparate effects of different modalities on central hemodynamics, arterial stiffness and cardiac function in CVD, we note several limitations. First, some studies had small sample sizes, and according to the subgroup analysis of exercise modalities, only one study investigated the effects of resistance exercise on LVEF or combined exercise on ASP, ADP and AIx in this subgroup analysis. These reports had no heterogeneity results for these outcomes in the numerical results. Larger-scale, good quality RCTs are needed for further investigating the effect of exercise on CVD. Second, a total of 10 articles (26.32%) had a long-term exercise intervention period (over 6 months), therefore, the long-term effects of different types of exercise on patients with CVD were not performed in this meta-analysis. Further studies are needed to explore the pathophysiological mechanisms of the relationship among central hemodynamics, arterial stiffness and cardiac function in CVD in response to different exercise training on the basis of controlling of external variables, such as age or disease.

Conclusions

Different exercise modalities have different effects on central hemodynamics, arterial stiffness and cardiac function in patients with CVD. Aerobic or resistance exercise significantly decreased ASP. Meanwhile, long-term aerobic exercise reduced AIx in patients with CVD. Aerobic exercise and combined exercise can effectively improve central arterial stiffness and cardiac function. The decreased central blood pressure in response to resistance exercise was mainly due to reservoir pressure reduction or improved microvascular perfusion. In contrast, improvement of central arterial stiffness and cardiac function in response to aerobic exercise and combined exercise was mainly due to their effects on cardiopulmonary fitness (VO2 peak related to oxygen delivery or SV) and endothelial function. However, some heterogeneity in the results of the papers considered in this review remains unexplained, partly due to a paucity of high-quality studies, especially ones concerned with the effects of combined exercise on central hemodynamics and arterial stiffness for the rehabilitation of CVD. Finally, we note that these findings have important implications in the rehabilitation of these patients, not only for the patients themselves but also for medical professionals, allowing individual treatments to be tailored to specific cardiovascular pathologies.

Supporting information

S1 Fig. Effect of aerobic exercise on heart rate-adjusted AIx in patients with CVD.

https://doi.org/10.1371/journal.pone.0200829.s003

(TIF)

Acknowledgments

We would like to thank Editor and Reviewers for their valuable comments and suggestions.

References

  1. 1. Lachat C, Otchere S, Roberfroid D, Abdulai A, Seret FMA, Milesevic J, et al. Diet and physical activity for the prevention of noncommunicable diseases in low-and middle-income countries: a systematic policy review. PLoS Med. 2013;10(6):e1001465. pmid:23776415
  2. 2. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. The lancet. 2013;380(9859):2224–60.
  3. 3. Mendis S, Davis S, Norrving B. Organizational Update The World Health Organization Global Status Report on Noncommunicable Diseases 2014; One More Landmark Step in the Combat Against Stroke and Vascular Disease. Stroke. 2015;46(5):e121–e2. pmid:25873596
  4. 4. Kohl HW, Craig CL, Lambert EV, Inoue S, Alkandari JR, Leetongin G, et al. The pandemic of physical inactivity: global action for public health. The Lancet. 2012;380(9838):294–305.
  5. 5. Dans A, Ng N, Varghese C, Tai ES, Firestone R, Bonita R. The rise of chronic non-communicable diseases in southeast Asia: time for action. The Lancet. 2011;377(9766):680–9.
  6. 6. Vanhees L, Rauch B, Piepoli M, van Buuren F, Takken T, Borjesson M, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III). Eur J Prev Cardiol. 2012;19(6):1333–56. pmid:22637740.
  7. 7. Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation. 2010;121(4):505–11. pmid:20083680.
  8. 8. Vlachopoulos C, Aznaouridis K, O’Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. European heart journal. 2010;31(15):1865–71. pmid:20197424
  9. 9. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. Journal of the American College of Cardiology. 2010;55(13):1318–27. pmid:20338492.
  10. 10. Montero D, Roche E, Martinez-Rodriguez A. The impact of aerobic exercise training on arterial stiffness in pre-and hypertensive subjects: a systematic review and meta-analysis. International journal of cardiology. 2014;173(3):361–8. pmid:24698257
  11. 11. Heffernan KS, Yoon ES, Sharman JE, Davies JE, Shih YT, Chen CH, et al. Resistance exercise training reduces arterial reservoir pressure in older adults with prehypertension and hypertension. Hypertension research: official journal of the Japanese Society of Hypertension. 2013;36(5):422–7. Epub 2012/12/14. pmid:23235716.
  12. 12. Cheetham C, Green D, Collis J, Dembo L, O’Driscoll G. Effect of aerobic and resistance exercise on central hemodynamic responses in severe chronic heart failure. Journal of Applied Physiology. 2002;93(1):175–80. pmid:12070202
  13. 13. Ashor AW, Lara J, Siervo M, Celis-Morales C, Mathers JC. Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials. PloS one. 2014;9(10):e110034. pmid:25333969
  14. 14. Montero D, Vinet A, Roberts CK. Effect of combined aerobic and resistance training versus aerobic training on arterial stiffness. International journal of cardiology. 2015;178:69–76. pmid:25464222
  15. 15. Huang C, Wang J, Deng S, She Q, Wu L. The effects of aerobic endurance exercise on pulse wave velocity and intima media thickness in adults: A systematic review and meta-analysis. Scandinavian journal of medicine & science in sports. 2016;26(5):478–87. pmid:26059748.
  16. 16. Miyachi M. Effects of resistance training on arterial stiffness: a meta-analysis. Br J Sports Med. 2013;47(6):393–6. pmid:22267567.
  17. 17. Croymans DM, Krell SL, Oh CS, Katiraie M, Lam CY, Harris RA, et al. Effects of resistance training on central blood pressure in obese young men. Journal of human hypertension. 2014;28(3):157–64. Epub 2013/09/06. pmid:24005959
  18. 18. Figueroa A. Effects of resistance training on central blood pressure and wave reflection in obese adults with prehypertension. Journal of human hypertension. 2014;28(3):143–4. pmid:24005960.
  19. 19. Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Cheng S, et al. Relations of Central Hemodynamics and Aortic Stiffness with Left Ventricular Structure and Function: The Framingham Heart Study. Journal of the American Heart Association. 2016;5(3):e002693. pmid:27016574.
  20. 20. Shim CY, Park S, Choi D, Yang WI, Cho IJ, Choi EY, et al. Sex differences in central hemodynamics and their relationship to left ventricular diastolic function. Journal of the American College of Cardiology. 2011;57(10):1226–33. pmid:21371640.
  21. 21. Cavalcante JL, Lima JA, Redheuil A, Al-Mallah MH. Aortic stiffness: current understanding and future directions. Journal of the American College of Cardiology. 2011;57(14):1511–22. pmid:21453829.
  22. 22. Gielen S, Schuler G, Adams V. Cardiovascular effects of exercise training: molecular mechanisms. Circulation. 2010;122(12):1221–38. pmid:20855669.
  23. 23. Sakuragi S, Abhayaratna WP. Arterial stiffness: methods of measurement, physiologic determinants and prediction of cardiovascular outcomes. International journal of cardiology. 2010;138(2):112–8. pmid:19473713.
  24. 24. Liao D. Arterial stiffness and the development of hypertension. Annals of Medicine. 2009;32(6):383–5.
  25. 25. Kitzman DW, Brubaker PH, Herrington DM, Morgan TM, Stewart KP, Hundley WG, et al. Effect of endurance exercise training on endothelial function and arterial stiffness in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. Journal of the American College of Cardiology. 2013;62(7):584–92. Epub 2013/05/15. pmid:23665370
  26. 26. Chrysohoou C, Angelis A, Tsitsinakis G, Spetsioti S, Nasis I, Tsiachris D, et al. Cardiovascular effects of high-intensity interval aerobic training combined with strength exercise in patients with chronic heart failure. A randomized phase III clinical trial. International journal of cardiology. 2015;179:269–74. pmid:25464463
  27. 27. Molmen-Hansen HE, Stolen T, Tjonna AE, Aamot IL, Ekeberg IS, Tyldum GA, et al. Aerobic interval training reduces blood pressure and improves myocardial function in hypertensive patients. European journal of preventive cardiology [Internet]. 2012; 19(2):[151–60 pp.]. pmid:21450580
  28. 28. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Bmj. 2011;343:d5928. pmid:22008217
  29. 29. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. British Medical Journal. 2003;327(7414):557–60. pmid:12958120
  30. 30. Higgins JPT G S. Cochrane Handbook for Systematic Reviews of Interventions. Hoboken, NJ: Wiley; 2011. 2011.
  31. 31. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629–34. pmid:9310563
  32. 32. Acanfora D, Scicchitano P, Casucci G, Lanzillo B, Capuano N, Furgi G, et al. Exercise training effects on elderly and middle-age patients with chronic heart failure after acute decompensation: A randomized, controlled trial. International journal of cardiology. 2016;225:313–23. Epub 2016/10/18. pmid:27750131.
  33. 33. Acar RD, Bulut M, Ergun S, Yesin M, Akcakoyun M. Evaluation of the effect of cardiac rehabilitation on left atrial and left ventricular function and its relationship with changes in arterial stiffness in patients with acute myocardial infarction. Echocardiography (Mount Kisco, NY). 2015;32(3):443–7. Epub 2014/07/23. pmid:25047089.
  34. 34. Adamopoulos S, Schmid JP, Laoutaris ID, Dendale P, Doulaptsis C, Kouloubinis A, et al. Combined aerobic/ventilatory muscle training versus aerobic training in patients with chronic heart failure. The VENT-HEFT trial: A prospective randomized multi-European trial. European heart journal. 2011;32:183-.
  35. 35. Aksoy S, Findikoglu G, Ardic F, Rota S, Dursunoglu D. Effect of 10-Week Supervised Moderate-Intensity Intermittent vs. Continuous Aerobic Exercise Programs on Vascular Adhesion Molecules in Patients with Heart Failure. American journal of physical medicine & rehabilitation / Association of Academic Physiatrists [Internet]. 2015; 94(10 Suppl 1):[898–911 pp.].
  36. 36. Andersen LJ, Randers MB, Hansen PR, Hornstrup T, Schmidt JF, Dvorak J, et al. Structural and functional cardiac adaptations to 6months of football training in untrained hypertensive men. Scandinavian journal of medicine & science in sports. 2014;24:27–35. pmid:24903081
  37. 37. Beck DT, Martin JS, Casey DP, Braith RW. Exercise training reduces peripheral arterial stiffness and myocardial oxygen demand in young prehypertensive subjects. American journal of hypertension. 2013;26(9):1093–102. Epub 2013/06/06. pmid:23736111
  38. 38. Beer M, Wagner D, Myers J, Sandstede J, Koestler H, Hahn D, et al. Effects of exercise training on myocardial energy metabolism and ventricular function assessed by quantitative phosphorus-31 magnetic resonance spectroscopy and magnetic resonance imaging in dilated cardiomyopathy. Journal of the American College of Cardiology. 2008;51(19):1883–91. pmid:18466804
  39. 39. Belardinelli R, Georgiou D, Scocco V, Barstow TJ, Purcaro A. Low intensity exercise training in patients with chronic heart failure. Journal of the American College of Cardiology. 1995;26(4):975–82. Epub 1995/10/01. pmid:7560627.
  40. 40. Bilinska M, Kosydar-Piechna M, Gasiorowska A, Mikulski T, Piotrowski W, Nazar K, et al. Influence of dynamic training on hemodynamic, neurohormonal responses to static exercise and on inflammatory markers in patients after coronary artery bypass grafting. Circ J. 2010;74(12):2598–604. Epub 2010/10/19. pmid:20953063.
  41. 41. Blumenthal JA, Sherwood A, Gullette EC, Babyak M, Waugh R, Georgiades A, et al. Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning. Arch Intern Med. 2000;160(13):1947–58. Epub 2000/07/11. pmid:10888969.
  42. 42. Brubaker PH, Moore JB, Stewart KP, Wesley DJ, Kitzman DW. Endurance exercise training in older patients with heart failure: results from a randomized, controlled, single-blind trial. Journal of the American Geriatrics Society [Internet]. 2009; 57(11):[1982–9 pp.]. pmid:20121952
  43. 43. Donley DA, Fournier SB, Reger BL, DeVallance E, Bonner DE, Olfert IM, et al. Aerobic exercise training reduces arterial stiffness in metabolic syndrome. Journal of applied physiology (Bethesda, Md: 1985). 2014;116(11):1396–404. Epub 2014/04/20. pmid:24744384
  44. 44. Dubach P, Myers J, Dziekan G, Goebbels U, Reinhart W, Muller P, et al. Effect of high intensity exercise training on central hemodynamic responses to exercise in men with reduced left ventricular function. Journal of the American College of Cardiology. 1997;29(7):1591–8. Epub 1997/06/01. pmid:9180124.
  45. 45. Ehlken N, Lichtblau M, Klose H, Weidenhammer J, Fischer C, Nechwatal R, et al. Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial. European heart journal. 2016;37(1):35–44. pmid:26231884
  46. 46. Faulkner J, Tzeng YC, Lambrick D, Woolley B, Allan PD, O’Donnell T, et al. A randomized controlled trial to assess the central hemodynamic response to exercise in patients with transient ischaemic attack and minor stroke. Journal of human hypertension. 2016. Epub 2016/09/30. pmid:27680390.
  47. 47. Figueroa A, Kalfon R, Madzima TA, Wong A. Whole-body vibration exercise training reduces arterial stiffness in postmenopausal women with prehypertension and hypertension. Menopause-the Journal of the North American Menopause Society. 2014;21(2):131–6. pmid:23715407
  48. 48. Fu T-C, Wang C-H, Lin P-S, Hsu C-C, Cherng W-J, Huang S-C, et al. Aerobic interval training improves oxygen uptake efficiency by enhancing cerebral and muscular hemodynamics in patients with heart failure. International journal of cardiology. 2013;167(1):41–50. pmid:22197120
  49. 49. Giallauria F, Acampa W, Ricci F, Vitelli A, Torella G, Lucci R, et al. Exercise training early after acute myocardial infarction reduces stress-induced hypoperfusion and improves left ventricular function. Eur J Nucl Med Mol Imaging. 2013;40(3):315–24. Epub 2012/12/12. pmid:23224706.
  50. 50. Giannuzzi P, Temporelli PL, Corra U, Tavazzi L, Grp E-CS. Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure results of the exercise in left ventricular dysfunction and chronic heart failure (ELVD-CHF) trial. Circulation. 2003;108(5):554–9. pmid:12860904
  51. 51. Guimaraes GV, Ciolac EG, Carvalho VO, D’Avila VM, Bortolotto LA, Bocchi EA. Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension. Hypertension research: official journal of the Japanese Society of Hypertension. 2010;33(6):627–32. Epub 2010/04/10. pmid:20379194.
  52. 52. Hambrecht R, Gielen S, Linke A, Fiehn E, Yu J, Walther C, et al. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: A randomized trial. Jama. 2000;283(23):3095–101. Epub 2000/06/24. pmid:10865304.
  53. 53. Huang SC, Wong MK, Lin PJ, Tsai FC, Fu TC, Wen MS, et al. Modified high-intensity interval training increases peak cardiac power output in patients with heart failure. European journal of applied physiology. 2014;114(9):1853–62. Epub 2014/06/02. pmid:24880226.
  54. 54. Iellamo F, Legramante JM, Massaro M, Raimondi G, Galante A. Effects of a residential exercise training on baroreflex sensitivity and heart rate variability in patients with coronary artery disease—A randomized, controlled study. Circulation. 2000;102(21):2588–92. pmid:11085961
  55. 55. Krustrup P, Randers MB, Andersen LJ, Jackman SR, Bangsbo J, Hansen PR. Soccer improves fitness and attenuates cardiovascular risk factors in hypertensive men. Medicine and science in sports and exercise. 2013;45(3):553–60. pmid:23059865
  56. 56. Lee YH, Park SH, Yoon ES, Lee C-D, Wee SO, Fernhall B, et al. Effects of Combined Aerobic and Resistance Exercise on Central Arterial Stiffness and Gait Velocity in Patients with Chronic Poststroke Hemiparesis. American journal of physical medicine & rehabilitation. 2015;94(9):687–95. pmid:25357149
  57. 57. Madden KM, Lockhart C, Cuff D, Potter TF, Meneilly GS. Aerobic training-induced improvements in arterial stiffness are not sustained in older adults with multiple cardiovascular risk factors. Journal of human hypertension. 2013;27(5):335–9. Epub 2012/09/07. pmid:22951625
  58. 58. Nualnim N, Parkhurst K, Dhindsa M, Tarumi T, Vavrek J, Tanaka H. Effects of swimming training on blood pressure and vascular function in adults> 50 years of age. The American journal of cardiology. 2012;109(7):1005–10. pmid:22244035
  59. 59. Oliveira NL, Ribeiro F, Silva G, Alves AJ, Silva N, Guimaraes JT, et al. Effect of exercise-based cardiac rehabilitation on arterial stiffness and inflammatory and endothelial dysfunction biomarkers: a randomized controlled trial of myocardial infarction patients. Atherosclerosis. 2015;239(1):150–7. Epub 2015/01/21. pmid:25602857.
  60. 60. PARNELL MM, HOLST DP. Exercise training increases arterial compliance in patients with congestive heart failure. Clinical Science. 2002;102(1):1–7. pmid:11749654
  61. 61. Seals DR, Tanaka H, Clevenger CM, Monahan KD, Reiling MJ, Hiatt WR, et al. Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness. Journal of the American College of Cardiology. 2001;38(2):506–13. Epub 2001/08/14. pmid:11499745.
  62. 62. Stewart KJ, Bacher AC, Turner KL, Fleg JL, Hees PS, Shapiro EP, et al. Effect of exercise on blood pressure in older persons: a randomized controlled trial. Archives of Internal Medicine. 2005;165(7):756–62. pmid:15824294
  63. 63. Su MY, Lee BC, Yu HY, Wu YW, Chu WC, Tseng WY. Exercise training increases myocardial perfusion in residual viable myocardium within infarct zone. Journal of magnetic resonance imaging: JMRI. 2011;34(1):60–8. Epub 2011/05/25. pmid:21608065.
  64. 64. Tang A, Eng JJ, Krassioukov AV, Madden KM, Mohammadi A, Tsang MY, et al. Exercise-induced changes in cardiovascular function after stroke: a randomized controlled trial. International journal of stroke: official journal of the International Stroke Society. 2014;9(7):883–9. Epub 2013/10/24. pmid:24148695.
  65. 65. Westhoff TH, Schmidt S, Gross V, Joppke M, Zidek W, van der Giet M, et al. The cardiovascular effects of upper-limb aerobic exercise in hypertensive patients. Journal of hypertension. 2008;26(7):1336–42. pmid:18551008
  66. 66. Roman MJ, Devereux RB, Kizer JR, Lee ET, Galloway JM, Ali T, et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study. Hypertension (Dallas, Tex: 1979). 2007;50(1):197–203. pmid:17485598.
  67. 67. Wang KL, Cheng HM, Chuang SY, Spurgeon HA, Ting CT, Lakatta EG, et al. Central or peripheral systolic or pulse pressure: which best relates to target organs and future mortality? Journal of Hypertension. 2009;27(3):461. pmid:19330899
  68. 68. Taaffe DR, Galvao DA, Sharman JE, Coombes JS. Reduced central blood pressure in older adults following progressive resistance training. Journal of human hypertension. 2007;21(1):96–8. pmid:17096007.
  69. 69. Miyachi M, Kawano H, Sugawara J, Takahashi K, Hayashi K, Yamazaki K, et al. Unfavorable effects of resistance training on central arterial compliance: a randomized intervention study. Circulation [Internet]. 2004; 110(18):[2858–63 pp.]. pmid:15492301
  70. 70. Kawano H, Tanimoto M, Yamamoto K, Sanada K, Gando Y, Tabata I, et al. Resistance training in men is associated with increased arterial stiffness and blood pressure but does not adversely affect endothelial function as measured by arterial reactivity to the cold pressor test. Experimental physiology. 2008;93(2):296–302. pmid:17911355.
  71. 71. Wildman RP, Mackey RH, Bostom A, Thompson T, Sutton-Tyrrell K. Measures of obesity are associated with vascular stiffness in young and older adults. Hypertension (Dallas, Tex: 1979). 2003;42(4):468–73. pmid:12953016.
  72. 72. Parker KH, Alastruey J, Stan GB. Arterial reservoir-excess pressure and ventricular work. Med Biol Eng Comput. 2012;50(4):419–24. pmid:22367750.
  73. 73. Zhang Y, Xu L, Zhang X, Yao Y, Sun Y, Qi L. Effects of different durations of aerobic exercise intervention on the cardiovascular health in untrained women: a meta-analysis and meta-regression. Journal of Sports Medicine & Physical Fitness. 2017.
  74. 74. Davies JE, Baksi J, Francis DP, Hadjiloizou N, Whinnett ZI, Manisty CH, et al. The arterial reservoir pressure increases with aging and is the major determinant of the aortic augmentation index. Am J Physiol Heart Circ Physiol. 2010;298(2):H580–6. pmid:20008272.
  75. 75. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. European heart journal. 2006;27(21):2588–605. pmid:17000623.
  76. 76. Stohr EJ, McDonnell B, Thompson J, Stone K, Bull T, Houston R, et al. Left ventricular mechanics in humans with high aerobic fitness: adaptation independent of structural remodelling, arterial haemodynamics and heart rate. The Journal of physiology. 2012;590(9):2107–19. pmid:22431336.
  77. 77. Mitchell GF, Conlin PR, Dunlap ME, Lacourciere Y, Arnold JM, Ogilvie RI, et al. Aortic diameter, wall stiffness, and wave reflection in systolic hypertension. Hypertension (Dallas, Tex: 1979). 2008;51(1):105–11. pmid:18071054.
  78. 78. Zhang Y, Xu L, Yao Y, Guo X, Sun Y, Zhang J, et al. Effect of short-term exercise intervention on cardiovascular functions and quality of life of chronic heart failure patients: A meta-analysis. Journal of Exercise Science & Fitness. 2016;14(2):67–75.
  79. 79. Van Craenenbroeck AH, Van Craenenbroeck EM, Van Ackeren K, Vrints CJ, Conraads VM, Verpooten GA, et al. Effect of Moderate Aerobic Exercise Training on Endothelial Function and Arterial Stiffness in CKD Stages 3–4: A Randomized Controlled Trial. American journal of kidney diseases: the official journal of the National Kidney Foundation. 2015;66(2):285–96. Epub 2015/05/12. pmid:25960303.
  80. 80. Li Y, Hanssen H, Cordes M, Rossmeissl A, Endes S, Schmidt-Trucksaess A. Aerobic, resistance and combined exercise training on arterial stiffness in normotensive and hypertensive adults: A review. European Journal of Sport Science. 2015;15(5):443–57. pmid:25251989
  81. 81. Brown MD, Dengel DR, Hogikyan RV, Supiano MA. Sympathetic activity and the heterogenous blood pressure response to exercise training in hypertensives. Journal of Applied Physiology. 2002;92(4):1434–42. pmid:11896007
  82. 82. Haykowsky MJ, Liang Y, Pechter D, Jones LW, McAlister FA, Clark AM. A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed. Journal of the American College of Cardiology. 2007;49(24):2329–36. pmid:17572248.
  83. 83. Belardinelli R, Georgiou D, Cianci G, Purcaro A. Effects of exercise training on left ventricular filling at rest and during exercise in patients with ischemic cardiomyopathy and severe left ventricular systolic dysfunction. American heart journal. 1996;132(1):61–70.
  84. 84. Belardinelli R, Georgiou D, Ginzton L, Cianci G, Purcaro A. Effects of moderate exercise training on thallium uptake and contractile response to low-dose dobutamine of dysfunctional myocardium in patients with ischemic cardiomyopathy. Circulation. 1998;97(6):553–61. pmid:9494025
  85. 85. C AJ, A S, R A, M A, M TE, B L, et al. Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. Circulation. 1992;85(6):2119. pmid:1591831
  86. 86. Crisafulli A, Piras F, Filippi M, Piredda C, Chiappori P, Melis F, et al. Role of heart rate and stroke volume during muscle metaboreflex-induced cardiac output increase: differences between activation during and after exercise. J Physiol Sci. 2011;61(5):385–94. pmid:21796398.